The identification and molecular characterization of B lymphocyte associated antigens in man and application of specific serological reagents to approach their functional roles in mediating the immune responses are the main objectives of this proposal. Initially, it is intended to generate monoclonal antibodies reactive with cells of human B lymphocyte lineage and biochemical characterize these target antigens. Long term culture cell lines derived from either patients with various lymphoid malignancies or from normal individuals by EB virus transformations will be used as a source of materials for initial characterization. The relation of these B cell associated surface antigens to other B cell associated functional markers such as the receptors for complement components, Epstein Barr virus, and hormones will be sought. The significance of these molecules as differentiation antigens and the nature of the cells expressing them will be examined in cells from normal and diseased states. Specific serological reagents including both the newly generated monoclonal antibodies and the previously obtained heteroantisera raised towards isolated surface components will be used in various in vitro functional assays to study the roles these antigens play in T-B cell interactions, B cell proliferation and maturation. With the availability of the specifc antibody probes to these B cell surface antigens, and the assays for B cell proliferation and maturation, the problem of in vitro B cell differentiation will be pursued. The signals required and bio-chemcial events involved in both cell proliferation and differentiation process will be investigated.